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. 2017 Apr 19;37(16):4405-4415.
doi: 10.1523/JNEUROSCI.2405-16.2017. Epub 2017 Mar 23.

Cholinergic, But Not Dopaminergic or Noradrenergic, Enhancement Sharpens Visual Spatial Perception in Humans

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Cholinergic, But Not Dopaminergic or Noradrenergic, Enhancement Sharpens Visual Spatial Perception in Humans

Caterina Gratton et al. J Neurosci. .
Free PMC article

Abstract

The neuromodulator acetylcholine modulates spatial integration in visual cortex by altering the balance of inputs that generate neuronal receptive fields. These cholinergic effects may provide a neurobiological mechanism underlying the modulation of visual representations by visual spatial attention. However, the consequences of cholinergic enhancement on visuospatial perception in humans are unknown. We conducted two experiments to test whether enhancing cholinergic signaling selectively alters perceptual measures of visuospatial interactions in human subjects. In Experiment 1, a double-blind placebo-controlled pharmacology study, we measured how flanking distractors influenced detection of a small contrast decrement of a peripheral target, as a function of target-flanker distance. We found that cholinergic enhancement with the cholinesterase inhibitor donepezil improved target detection, and modeling suggested that this was mainly due to a narrowing of the extent of facilitatory perceptual spatial interactions. In Experiment 2, we tested whether these effects were selective to the cholinergic system or would also be observed following enhancements of related neuromodulators dopamine or norepinephrine. Unlike cholinergic enhancement, dopamine (bromocriptine) and norepinephrine (guanfacine) manipulations did not improve performance or systematically alter the spatial profile of perceptual interactions between targets and distractors. These findings reveal mechanisms by which cholinergic signaling influences visual spatial interactions in perception and improves processing of a visual target among distractors, effects that are notably similar to those of spatial selective attention.SIGNIFICANCE STATEMENT Acetylcholine influences how visual cortical neurons integrate signals across space, perhaps providing a neurobiological mechanism for the effects of visual selective attention. However, the influence of cholinergic enhancement on visuospatial perception remains unknown. Here we demonstrate that cholinergic enhancement improves detection of a target flanked by distractors, consistent with sharpened visuospatial perceptual representations. Furthermore, whereas most pharmacological studies focus on a single neurotransmitter, many neuromodulators can have related effects on cognition and perception. Thus, we also demonstrate that enhancing noradrenergic and dopaminergic systems does not systematically improve visuospatial perception or alter its tuning. Our results link visuospatial tuning effects of acetylcholine at the neuronal and perceptual levels and provide insights into the connection between cholinergic signaling and visual attention.

Keywords: acetylcholine; attention; dopamine; norepinephrine; pharmacology; visuospatial perception.

Figures

Figure 1.
Figure 1.
Experimental timeline. A, Experiment 1 contrasted the effects of cholinergic enhancement with donepezil (D) against placebo (P) in a within-subject, double-blind, placebo-controlled experiment with five separate sessions, including two refresher sessions to refamiliarize subjects with the task and to equate recent experience with the task for D and P pharmacological sessions. B, Experiment 2 examined the effects of dopaminergic enhancement (with bromocriptine [B]) and noradrenergic enhancement (with guanfacine [G]) in the same visual target detection task. Experiment 2 was also a within-subject, double-blind, placebo-controlled experiment and contained four experimental sessions, with a refresher period at the start of each pharmacological session, well before the administered drugs had any significant effects.
Figure 2.
Figure 2.
Task design. Each trial of the task began with a cue pointing to either the left or right top quadrant that indicated the location of the subsequent stimulus display, consisting of a low-contrast target flanked by high-contrast distractors (shown enlarged in inset, with white borders thickened for visualization). The critical manipulation was the distance between target and flankers, which varied between 0.2 and 2.0 degrees of visual angle. The participants' task was to determine whether a slight contrast decrement occurred in the target at some point during the display period (50% probability). The magnitude of the contrast decrement was adaptively varied from trial to trial to determine the threshold for 75% target detection accuracy.
Figure 3.
Figure 3.
Experiment 1. Effects of donepezil on target–flanker interactions in visual perception. A, The effect of target–flanker distance on sensitivity of contrast decrement detection after taking a donepezil or a placebo pill. B, The difference between sensitivity for donepezil and placebo conditions at different target–flanker distances. Compared with placebo, donepezil increased sensitivity, especially at intermediate (0.8 degree) distances. Error bars indicate SEM (A) across participants and (B) across participants for the donepezil-placebo difference. **p < 0.01.
Figure 4.
Figure 4.
Experiment 1. Modeling effects of donepezil on facilitatory and suppressive target–flanker interactions. A, A DoG curve (G1–G2, right) was fit to the data with four parameters: the amplitude (A1) and width (S1) of the broad facilitatory Gaussian (G1, gray line) and the amplitude (A2) and width (S2) of the narrower suppressive Gaussian (G2, black dashed line) separately for placebo and donepezil sessions. B, The cholinergic enhancement effect on each parameter is displayed as a contrast index (drug − placebo/drug + placebo). Positive values indicate that the drug increased amplitude/width, and negative values indicate that the drug decreased amplitude/width for each Gaussian. Compared with placebo, donepezil significantly decreased the spatial extent of the facilitatory Gaussian (S1). **p < 0.01.
Figure 5.
Figure 5.
Experiment 2. Effects of bromocriptine and guanfacine on target–flanker interactions. A, The effect of target–flanker distance on sensitivity of contrast decrement detection after taking placebo (white circles), bromocriptine (light gray), or guanfacine (dark gray). Data points have been slightly offset from one another to facilitate visualization, but target–flanker distances were the same in all drug conditions. B, Paired differences between bromocriptine and placebo sessions. Bromocriptine weakly modulated target–flanker interactions at different distances, tending to decrease sensitivity at intermediate distances. C, Paired differences between guanfacine and placebo sessions. Guanfacine had no significant effect on target detection, although participants showed a trend toward impaired overall performance.
Figure 6.
Figure 6.
Experiment 2. Modeling effects of bromocriptine and guanfacine on facilitatory and suppressive target–flanker interactions. Drug effects on the Gaussian parameter values for bromocriptine and placebo (A) and guanfacine and placebo (B) sessions from Experiment 2. Unlike the effects of cholinergic enhancement (Fig. 4B), no significant differences were seen for any parameters for either bromocriptine or guanfacine.

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